A1 Refereed original research article in a scientific journal
Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression
Authors: Võsa Urmo, Claringbould Annique, Westra Harm-Jan, Bonder Marc Jan, Deelen Patrick, Zeng Biao, Kirsten Holger, Saha Ashis, Kreuzhuber Roman, Yazar Seyhan, Brugge Harm, Oelen Roy, de Vries Dylan H., van der Wijst Monique G. P., Kasela Silva, Pervjakova Natalia, Alves Isabel, Favé Marie-Julie, Agbessi Mawussé, Christiansen Mark W., Jansen Rick, Seppälä Ilkka, Tong Lin, Teumer Alexander, Schramm Katharina, Hemani Gibran, Verlouw Joost, Yaghootkar Hanieh, Flitman Reyhan Sönmez, Brown Andrew, Kukushkina Viktorija, Kalnapenkis Anette, Rüeger Sina, Porcu Eleonora, Kronberg Jaanika, Kettunen Johannes, Lee Bernett, Zhang Futao, Qi Ting, Hernandez Jose Alquicira, Arindrarto Wibowo, Beutner Frank, Dmitrieva Julia, Elansary Mahmoud, Fairfax Benjamin P., Georges Michel, Heijmans Bastiaan T., Hewitt Alex W., Kähönen Mika, Kim Yungil, Knight Julian C., Kovacs Peter, Krohn Knut, Li Shuang, Loeffler Markus, Marigorta Urko M., Mei Hailang, Momozawa Yukihide, Müller-Nurasyid Martina, Nauck Matthias, Nivard Michel G., Penninx Brenda W. J. H., Pritchard Jonathan K., Raitakari Olli T., Rotzschke Olaf, Slagboom Eline P., Stehouwer Coen D. A., Stumvoll Michael, Sullivan Patrick, ’t Hoen Peter A. C., Thiery Joachim, Tönjes Anke, van Dongen Jenny, van Iterson Maarten, Veldink Jan H., Völker Uwe, Warmerdam Robert, Wijmenga Cisca, Swertz Morris, Andiappan Anand, Montgomery Grant W., Ripatti Samuli, Perola Markus, Kutalik Zoltan, Dermitzakis Emmanouil, Bergmann Sven, Frayling Timothy, van Meurs Joyce, Prokisch Holger, Ahsan Habibul, Pierce Brandon L., Lehtimäki Terho, Boomsma Dorret I., Psaty Bruce M., Gharib Sina A., Awadalla Philip, Milani Lili, Ouwehand Willem H., Downes Kate, Stegle Oliver, Battle Alexis, Visscher Peter M., Yang Jian, Scholz Markus, Powell Joseph, Gibson Greg, Esko Tõnu, Franke Lude; BIOS Consortium (BIOS Consortium); i2QTL Consortium (i2QTL Consortium)
Publisher: NATURE PORTFOLIO
Publication year: 2021
Journal: Nature Genetics
Journal name in source: NATURE GENETICS
Journal acronym: NAT GENET
Volume: 53
Issue: 9
First page : 1300
Last page: 1310
Number of pages: 22
ISSN: 1061-4036
eISSN: 1546-1718
DOI: https://doi.org/10.1038/s41588-021-00913-z
Web address : https://www.nature.com/articles/s41588-021-00913-z
Trait-associated genetic variants affect complex phenotypes primarily via regulatory mechanisms on the transcriptome. To investigate the genetics of gene expression, we performed cis- and trans-expression quantitative trait locus (eQTL) analyses using blood-derived expression from 31,684 individuals through the eQTLGen Consortium. We detected cis-eQTL for 88% of genes, and these were replicable in numerous tissues. Distal trans-eQTL (detected for 37% of 10,317 trait-associated variants tested) showed lower replication rates, partially due to low replication power and confounding by cell type composition. However, replication analyses in single-cell RNA-seq data prioritized intracellular trans-eQTL. Trans-eQTL exerted their effects via several mechanisms, primarily through regulation by transcription factors. Expression of 13% of the genes correlated with polygenic scores for 1,263 phenotypes, pinpointing potential drivers for those traits. In summary, this work represents a large eQTL resource, and its results serve as a starting point for in-depth interpretation of complex phenotypes.Analyses of expression profiles from whole blood of 31,684 individuals identify cis-expression quantitative trait loci (eQTL) effects for 88% of genes and trans-eQTL effects for 37% of trait-associated variants.
